This article is a translation of the Dutch interview

The European Union is working on new overarching legislation on pharmaceuticals. A legislative proposal was made public in April 2023 and the European Parliament gave its assent on 10 April 2024. The proposal is now before the Council of Ministers for decision. To support the Dutch feedback on this proposal, a quick scan was carried out. A key conclusion is that there should be room for regulatory experiments (‘sandboxes’).

‘The existing European regulation still works quite well, but especially with a view to the future, new rules are needed,’ says Prof Dr Bert Leufkens, emeritus professor of regulatory science. The quick scan was commissioned by the Ministry of Health, Welfare and Sport and carried out by Technopolis, partly based on interviews with various stakeholders.

The project was part of the ZonMw programme Regulatory Pandemic Preparedness, Bert chaired the quickscan’s guidance committee. ‘It is important that regulations are future-proofed to facilitate the deployment of innovative methods and the assessment of innovative therapies so that they become available to patients. That is why VWS would like good input to take into account in the negotiations on this new European legislation,’ says Marlous Kooijman, who served on the guidance committee from FAST.
The Netherlands’ input in the new legislation has a certain authority, because our country has a good reputation in the field of regulatory science and health technology assessment. Leufkens: ‘We no longer have so many big pharmaceutical companies, but our country is strong in biotechnology and innovative developments’.

Background
Leufkens sees three drivers for the new bill: substantive developments, Europe’s competitive position in the world and the availability of medicines across the EU. ‘Content-wise, there are of course many scientific and clinical developments, such as CRISPR-CAS, oligonucleotides, personalised medicine, AI and new ways of handling data,’ Leufkens said. ‘Europe has a lot of knowledge, but international competition is fierce, not only from the United States, but also increasingly from Asian countries and South America. Regulations can either facilitate or inhibit innovation. And the availability of treatments is an important issue politically in Europe, because a drug available in the Netherlands or Germany is not automatically available in Romania as well.’ ‘In addition, tackling antimicrobial resistance, developing therapies for rare diseases and children and sustainability are also important themes,’ Kooijman adds.

Five themes
The Technopolis report ‘Eye to the future: is the proposed EU General Pharmaceutical Legislation ready to support pharmaceutical innovation?’, sent to the Lower House on 8 July, identifies five key themes for VWS in the negotiations on the new regulations. The first theme is perhaps the most important: it deals with room for new forms of scientific evidence when authorising new drugs. Leufkens: ‘The proposal pays attention to possibilities for sandboxes, in which other forms of (pre-)clinical evidence can be taken into account in the decision to admit a drug to the market. This is a controversial topic. On the one hand, there are regular newspaper articles that are very critical of the current authorisation policy, stating that sometimes drugs are now being authorised for which there is insufficient evidence of their effectiveness and safety. On the other hand, you don’t want to close the evidence requirements completely, especially for innovative treatments for rare diseases, for example. The Technopolis report states that there should be room for sandboxes.’ Kooijman: ‘For successful implementation of sandboxes, it is important to clarify what the concrete interpretation and preconditions of such sandboxes will be. But the idea of a sandbox, of experimental space, is absolutely necessary, especially for developing therapies that do not fit well within standard frameworks, such as therapies based on innovative technology or for very rare diseases. This also applies to using Real World Data and Real World Evidence, i.e. the outcomes of non-study treatments, when assessing whether a drug meets expectations. From FAST, we are experimenting with the field with this.’

Hospital exemption
Another topic that is highly relevant from FAST’s perspective concerns the local preparation of drugs and ATMPs. This involves preparation within the pharmacy (or associated GMP facility) of an umc or hospital, without a marketing authorisation through the central European procedure, a so-called hospital exemption. Such local compounding can be very important for tailor-made treatments and for ensuring the availability of medicines, especially for rare conditions. But here, too, a nuanced approach is desirable, especially at the European level. After all, these are largely high-value complex production processes with little margin for imperfections. Leufkens: ‘A challenge for decentralised preparation is that quality may vary between decentralised production sites, among themselves and with pharmaceutical companies. On this point, there are also still quite large differences between European countries. I think we have very good facilities here in the Netherlands, but that level is not achieved in all European countries. That is why the Technopolis report advocates that countries should be allowed to set additional requirements and introduce rules on this point.’ Kooijman: ‘Another aspect that the report names is the possibility of resupplying products to other healthcare facilities and perhaps even to other countries. The challenge, of course, will be to give the hospital exemption, intended in principle as an exception, a broader meaning without violating the intentions of the ATMP regulation.

Comments
The quick scan identifies many other aspects, including the proposals to reorganise the European Medicines Agency EMA. While a critical look at the EMA’s various committees can certainly be useful, Leufkens warns against too radical a reorganisation: ‘It is very important that the member states and their national organisations remain sufficiently involved in the EMA. Otherwise, it will be perceived as a remote bureaucratic moloch, with all its drawbacks.’
The topic of drug repurposing (using registered drugs for new indications) also receives explicit attention in the Technopolis report. Kooijman: ‘An important point of attention in the report is, for example, that there will be more room for non-commercial parties, such as academic groups to submit evidence that a drug is also suitable for another indication. But there are concerns that the proposals as they stand have unwanted consequences. For example, the mandatory addition of new indications to the label could lead to a manufacturer deciding to withdraw the drug from the market. ‘The intention is good, the proposals are aimed at enabling drug repurposing, but there are reservations about the plans as they stand.’

The report can be downloaded from 8 July on How future-proof is the proposed revised EU drug (zonmw.nl). Leufkens: ‘I sincerely hope that the ministry will let these voices be heard in the discussions about the new regulations. Innovation remains incredibly important for all those groups of patients for whom no good treatment is yet available. Just think of the growing problem of antimicrobial resistance, a topic that is also explicitly mentioned by the European Commission. New European regulations can help to give innovation better opportunities, but also to ensure greater availability.’

For more information on the procedure for creating European legislation, see: What is the procedure for creating European legislation? – Europe decentralised